tbuckley/cabot-search huggingface dataset:
Abstract 14438: Longitudinal Real World Study of Blood Pressure and Cerebral Arterial Stenosis on Elderly Cognitive Impairment Based on the Artificial Intelligence Analysis of Serial Brain Magnetic Resonance Angiography
Authors: Shasha Sun, Xian Xu, Yanfeng Zhou, Longbiao Cui, Jiacheng Jiang, Li Fan, Feng Cao
Journal: Circulation (2022)

Background: Abnormal blood pressure (BP) is one of the most common modified risk factors for the development of cognitive impairment (CI) with increasing aging population. Objective: This study aims to investigate the association between risk factors and CI in elderly patients based on artificial intelligence (AI) analysis of BP measurements and brain magnetic resonance angiography (MRA). Methods: A total of 3221 elderly individuals undergone brain MRA were recruited into the nested case-control study from 2007 to 2021. Patients were divided into two groups according to diagnosis with or without CI. Data were collected before diagnosing CI. The stenosis rate of cerebral arteries was calculated by AI analysis of brain MRA. Four machine learning modalities were applied to establish predictive models. Results: A total of 416 cases (mean age 84.47 ± 6.50 years old) with or without CI were finally recruited into the study after matching with age and gender. Mean follow-up time was 3.46 ± 3.19 years. The number of BP measurements was 56.98 ± 77.94 times. In the univariate logistic regression model, high systolic blood pressure (SBP) (OR 1.029, 95% CIs 1.010-1.049), pulse pressure (PP) (OR 1.043, 95% CIs: 1.021-1.065) and pulse pressure index (PPI) (OR 3588.920, 95% CIs: 44.392-290148.336) increased the risk of CI. Based on various mean BP parameters, the predictive ability of the support vector machine (SVM) was improved after adding cerebral arterial stenosis rate (AUC 0.781, 95% CIs 0.639~0.923). Conclusion: Abnormal SBP, PP and PPI were risk factors for CI in the elderly Chinese population. Adding the cerebral arterial stenosis rate of internal carotid artery and posterior cerebral artery the predictive ability of SVM model of various mean BP parameters for the risk of CI was improved.
Abstract 14745: Recurrent Cardiogenic Shock Secondary to Shoshin Beriberi in s Patient With Heavy Alcohol Use
Authors: Karla M Asturias, Matthew Sangoi, Paul Kinniry, Alan Gandler
Journal: Circulation (2022)

Introduction: Thiamine is an essential enzyme cofactor in cellular metabolism. Its deficiency can manifest as wet beriberi with high-output heart failure. Its more severe and fulminant form is known as shoshin beriberi, characterized by cardiogenic shock, hemodynamic collapse, and multiorgan failure. Case Description: A 67-year-old male presented with dyspnea on exertion and orthopnea. On exam, he was tachycardic and cold to the touch. Initial workup showed metabolic acidosis, elevated lactate, acute kidney and liver injury, and elevated NT proBNP. ECG showed atrial fibrillation with RVR. His past medical history included heavy alcohol use and a similar presentation two years prior with new-onset heart failure complicated by shock and acute kidney injury, requiring CRRT. At that time, he improved with high-dose thiamine and decompensation was attributed to shoshin beriberi. Shortly after admission, the patient developed worsening shock, with liver failure, renal failure, and DIC. He was started on pressors, broad-spectrum antibiotics, high-dose thiamine and CRRT. TTE showed biventricular dysfunction and global hypokinesis with LVEF of 20%. Hemodynamic monitoring was consistent with cardiogenic shock. Infectious workup was negative. Within 96h of the initiation of thiamine, the patient’s mental status and hemodynamics significantly improved, with resolution of cardiogenic shock. He remained hemodynamically stable, his laboratory abnormalities improved, and he was started on GDMT. He required intermittent HD for several months, after which it was discontinued. He later underwent LHC that showed nonobstructive CAD. Discussion: The diagnosis of shoshin beriberi is challenging and requires a high index of suspicion for presumed thiamine deficiency, particularly in critically ill patients with many comorbidities. An empiric therapeutic trial of thiamine supplementation in this group of patients can lead to improvement of hemodynamics within hours to days, as in this case. Even though his LVEF has not yet fully recovered, we suspect that his presentation was due to an acute-on-chronic insult, in the setting of alcohol-induced cardiomyopathy. To the best of our knowledge, this is the first report of recurrent shoshin beriberi in the literature.
Abstract 15792: Unchecked Cytokinesis Generates Highly Proliferative Mononuclear Cardiomyocytes at the Expense of Contractility
Authors: Nicholas T Lam, Waleed M Elhelaly, Ivan Menendez-Montes, Ching-Cheng Hsu, Ngoc Nguyen, Feng Xiao, Mahmoud S Ahmed, Shujuan Li, Suwannee Thet, Lior Zangi, Hesham A Sadek
Journal: Circulation (2022)

Introduction: A few days after birth in mouse cardiomyocytes, DNA synthesis occurs without cytokinesis leading to the majority of cardiomyocytes becoming binuclear instead of generating 2 daughter cells with one nucleus each. This results in cell cycle arrest of cardiomyocytes and the mouse heart is no longer able to regenerate. Hypothesis: A long-standing unanswered question in the field is whether multinucleation of cardiomyocytes is a result of cytokinesis failure. Methods and Results: To address this, we generated several transgenic mouse models to determine whether forced induction of cardiomyocyte cytokinesis generates mononuclear cardiomyocytes and restores the endogenous regenerative properties of the myocardium. We focused on two complementary regulators of cytokinesis, namely Polo-like kinase 1 (Plk1) and epithelial cell-transformation sequence 2 (Ect2), Here we report that cardiomyocyte-specific transgenic overexpression of constitutively active Plk1(T210D) alone promotes mitosis and cytokinesis in adult hearts, while overexpression of Ect2 alone promotes cytokinesis. Intriguingly, cardiomyocyte-specific overexpression of both Plk1(T210D) and Ect2 concomitantly (double transgenic) prevents binucleation of cardiomyocytes postnatally and results in widespread cardiomyocyte mitosis, cardiac enlargement, contractile failure and death before two weeks of age. Similarly, high-dose doxycycline inducible cardiomyocyte-specific overexpression of both proteins (inducible double transgenic) in the adult heart results in reversible widespread cardiomyocyte mitosis, cardiac enlargement, and contractile failure, while low-dose transient induction also results in significant cardiomyocyte proliferation and lower ejection fraction that is reversible after doxycycline is removed. Finally, we show that transient low-dose induction of both genes in adults improves left ventricular systolic function following myocardial infarction. Conclusion: Collectively, these results demonstrate that cytokinesis failure mediates cardiomyocyte multinucleation and cell cycle exit of postnatal cardiomyocytes but may be a protective mechanism to preserve the contractile function of the myocardium.
Abstract 15233: Risk of Venous Thromboembolism and Nonrheumatic Valvular Heart Disease in Patients With Elevated Lipoprotein(a): A Retrospective Cohort Study
Authors: Evan S Bloch, Gai Elhanan, William J Metcalf, Joseph Grzymski
Journal: Circulation (2022)

Introduction: Higher Lipoprotein(a) (Lp(a)) levels are known to be associated with increased risk of ASCVD. However, the effect of elevated Lp(a) on other cardiovascular (CV) diseases is largely unknown. We sought to identify whether Lp(a) level might be a risk factor for non-atherosclerotic CV conditions. Methods: Using data from the Healthy Nevada Project (HNP), a population genetic study based in Northern Nevada with &gt;52,000 participants, we conducted a retrospective analysis of all participants with recorded Lp(a) levels. An exploratory analysis was performed examining associations between elevated Lp(a) levels and various CV conditions based on ICD 10 codes. Elevated Lp(a) was defined as &gt;50 mg/dl or &gt;125 nmol/L. We examined ICD 10 codes related to venous thromboembolic (VTE) disease and non-rheumatic valvular heart disease (VHD). A Fisher’s Exact Test was performed to assess the significance of these associations. Results: Out of 4,010 HNP participants (age: 62±30; 42.7% female) with an Lp(a) result, 881 had elevated Lp(a), with incidence ~7% higher (~30% vs. ~23%) in Black, Pacific, and Native American groups. Of those with elevated Lp(a) levels, 96 (10.9%) had diagnoses (dxs) of VTE vs. 270 of 3129 (8.6%) participants with normal Lp(a) (p=0.046). Specifically, 9.76% of elevated Lp(a) participants vs. 7.51% of normal Lp(a) participants had dxs of DVT (p=0.035). No significant difference was found between elevated Lp(a) and PE. Additionally, 227 (25.8%) participants with elevated Lp(a) had VHD dxs compared to 593 (18.9%) participants from the normal Lp(a) cohort (p=0.0001). Specifically, 14.98% of elevated Lp(a) participants vs. 10.48% of normal Lp(a) participants had Aortic VHD (p=0.0003), and 14.87% of elevated Lp(a) participants vs. 10.35% normal Lp(a) participants had Mitral VHD (p=0.0003). No significant association was found between elevated Lp(a) and pulmonic or tricuspid VHD. Less novel but significant associations between elevated Lp(a) and Stroke (p=0.046) and CAD (p=0.0001) were also observed. Conclusions: In our study, elevated Lp(a) levels were significantly associated with increased risk of VTE and nonrheumatic VHD. An examination of these risks in association with germline genetic studies of ASCVD in the HNP is ongoing.
Abstract 14489: Non-ST-Elevation Myocardial Infarction in a Transgender Woman: A Case Report and Perspective Into an Emerging High-Risk Population
Authors: Afif Hossain, Perry Wengrofsky, Boniface Malangu, Parul Kakar, Qaisra Y Saeed, Julius Gardin
Journal: Circulation (2022)

Clinical Case: A 37-year-old transgender (TG) woman off gender-affirming hormonal therapy (GAHT) presented with substernal chest pain radiating to the left arm, worse with exertion and relieved with res. She was hypertensive and tachycardic on admission. Initial bloodwork revealed an elevated troponin I of 0.57 ng/mL, which peaked at 1.48 ng/mL. EKG on admission showed hyperacute T waves in the anterior leads without ST elevation (see Figure 1). She was diagnosed with non-ST elevation myocardial infarction (NSTEMI) and taken for left heart catheterization (LHC). Decision-Making: TTE showed preserved LVEF and basal inferior, basal inferolateral, basal anterolateral and mid-anterolateral hypokinesis. LHC showed proximal-to-mid right coronary artery (RCA) occlusion. After failed aspiration thrombectomy indicating calcified plaque, two overlapping drug-eluting stents (DES) were successfully deployed with restoration of flow. She was discharged home on aspirin, ticagrelor, atorvastatin, and carvedilol. Discussion: Despite a recent push to increase awareness, research and healthcare equality specific to lesbian, gay, bisexual, transgender, and queer (LGBTQ+) patients, a significant gap persists. Specifically, stress, inflammation, dyslipidemia, and thromboembolism predispose this understudied population to increased coronary artery disease (CAD) and myocardial infarction (MI). Accordingly, greater effort needs to be taken to mitigate preventable cardiac morbidity and mortality in this patient population. Conclusion: CAD in LGBTQ+ adults is well studied. However, there are few published studies on CAD specifically among TG men and women. National cross-sectional data highlights this disproportionate risk of CAD and MI among TG men and women relative to their cisgender female and male peers, a healthcare disparity recently emphasized by the AHA. Consequently, care must be taken to eliminate these aforementioned inequalities.
Abstract 14622: Macrophage Dectin-1 Targeted Photoactivation Promotes Inflammation Resolution With Stabilization of the High-Risk Atheroma as Serially Assessed by Intravascular OCT-NIRF Imaging
Authors: Jin Hyuk Kim, Yeon Hoon Kim, Jae Won Ahn, Hyun Jung Kim, Ryeong Hyun Kim, Joon Woo Song, Ye Hee Park, Hyeong Soo Nam, Dong Oh Kang, Hongki Yoo, Kyeongsoon Park, Jin W Kim
Journal: Circulation (2022)

Backgrounds: Atherosclerosis is a chronic inflammatory disease causing a fatal plaque rupture and its key aspect is a failure to resolve inflammation. We hypothesized that macrophage targeted near-infrared fluorescence (NIRF) emitting photoactivation could simultaneously in vivo assess the inflamed high-risk plaques and facilitate the inflammation resolution. Method and results: We newly synthesized a Dectin-1 targeted photoactivatable theranostic agent by the chemical conjugation of photosensitizer chlorin e6 (Ce6) and Dectin-1 ligand laminarin (LAM-Ce6). Intravascular photoactivation through a customized fiber-based diffuser effectively reduced inflammation in the targeted plaques 4 weeks after LAM-Ce6 administration as serially assessed by dual-modal optical coherence tomography (OCT)-NIRF catheter imaging. The number of TUNEL-positive apoptotic macrophages peaked at 1 day after laser irradiation, and then resolved until 4 weeks. One hour after the light therapy, autophagy was strongly augmented with the formation of autophagolysosomes revealed by co-localization of enhanced microtubule-associated protein light-chain 3 (LC3) and lysosome-associated membrane protein 2 (LAMP2) expressions in the plaques (Figure). LAM-Ce6 photoactivation increased the TUNEL/RAM11- and MerTK-positive cells in the plaques, suggestive of enhanced efferocytosis. In line with inflammation resolution, photoactivation reduced the plaque burden with collagen-rich fibrotic replacement via TGF-β pathway confirmed by corroborative immunostainings ( p &lt;0.01). Conclusions: OCT-NIRF imaging-guided macrophage Dectin-1 targetable photoactivation could stabilize the inflamed high-risk plaques by autophagy-mediated inflammation resolution and TGF-β dependent fibrotic replacement. This novel targeted photoactivation will offer new opportunity for the catheter based theranostic strategy.
Abstract 14556: Deep Phenotyping APOC3 Knockouts in a Population With High Consanguinity
Authors: Shareef Khalid, Maleeha Z Khan, Liya Wu, Muhammad Jahanzaib, Subhan Saeed, M. Rehan Mian, Muhammad Bilal Liaqat, Asif Rasheed, John S Millar, Daniel J Rader, Danish Saleheen
Journal: Circulation (2022)

Apolipoprotein C-III (APOC3) plays an integral role in the regulation of triglyceride-rich lipoproteins, by inhibiting the clearance of triglycerides carried by VLDL and chylomicron remnants in the blood. Prior work has shown that heterozygous loss of function (LOF) carriers of APOC3 have lower triglyceride levels and a lower risk of coronary artery disease (CAD). The quantitative impact of disease risk remains unknown in complete knockouts (KOs). Additionally, the effects and safety implications of complete APOC3 LOF have not been characterized. APOC3 inhibition is an active therapeutic strategy to lower CAD risk; hence these questions have therapeutic relevance. Among 37,244 unrelated sequenced individuals, including 19,681 cases of myocardial infarction (MI), in the Pakistan Genomic Resource - a biobank with high levels of consanguinity - we identified 207 heterozygous LOF carriers and 14 KOs. As expected, the KOs had undetectable APOC3 levels. We also observed a decrease in plasma triglycerides (P = 9E-85), VLDL-C levels (P = 2E-73), APOE levels (P = 5.4E-9) and an increase in HDL-C levels (P = 1E-34) and APOA1 levels (P = 6E-5) consistent with a gene-dosage effect. We observed a significant decrease in the risk of MI among heterozygous carriers (P = 0.01); however, we did not observe any protection from MI risk in complete KOs. Conversely, we observed a non-significant increase in the risk of MI in complete KOs compared to non-carriers; of the 14 knockouts identified, 9 were found to have MI. The loss of protection against MI could not be explained by the genetic background or by the increase in levels of homozygosity of the KOs. By recalling complete KOs and their family members, we were able to identify and phenotype an additional 33 complete KOs and 152 heterozygotes and assess other safety concerns related to complete APOC3 inhibition (i.e., glucose intolerance, fat content in the liver, etc.). In conclusion, by leveraging a highly consanguineous cohort, we have identified and phenotyped APOC3 KOs that have, hitherto, not been identified elsewhere. We did not observe APOC3 LOF to confer protection in complete KOs and observed other biomarker and phenotypic associations; these findings should inform existing therapeutic programs targeting APOC3.
Abstract 14689: Evaluation of Left Myocardial Mechanics in Pediatric Heart Transplant Patients by Speckle Tracking Echocardiography
Authors: Yuji Xie, Shuangshuang Zhu, Yiwei Zhang, Anjun Wu, Chenchen Sun, Mingxing Xie, Li Zhang
Journal: Circulation (2022)

Objective: The aim of this study was to evaluate the left myocardial mechanics in pediatric heart transplant (PHT) patients after heart transplantation by three- dimensional speckle tracking echocardiography (3D-STE). Method: We retrospectively analyzed thirty-eight pediatric patient who underwent orthotopic heart transplantation from January, 2015 to December, 2021 at Union Hospital, Tongji Medical College, Huazhong University of Science and Technology. Clinical characteristics and conventional echocardiographic indices were described. 3D-STE were used to analyze myocardial mechanics in thirty-eight PHT patients. Left ventricular strain and rotational indices at 6 month and 1 year after heart transplant were obtained. Differences between left ventricular myocardial mechanic indices at 6 months and 1 year after heart transplant were analyzed and compared with normal reference range. Results: There were no statistically significant difference of LVGLS, LVGCS, LVGRS, 3D-apical peak rotation, 3D-basal peak rotation, 3D-peak twist, and 3D-peak torsion in PHT patients between 6 months and 1 year after heart transplantation( P &gt;0.05). Compared with 3D strain normal reference, 3D-LVGLS decreased and 3D-LVGCS increased in PHT patients at 6 months after transplantation( P &lt;0.05). Compared with 3D rotational normal reference, 3D-peak twist and 3D-peak torsion increased at 6 months after transplantation( P &lt;0.05). Conclusion: Compared with normal reference range, strain parameters were decreased and rotational parameters were increased. The study provided evidence for further investigations in establishing normal reference range of left ventricular myocardial mechanics in PHT patients and post-transplantation management of PHT patients.
Abstract 15242: Donor-Derived Chagas Disease Masquerading as Acute Heart Transplant Rejection
Authors: Ehsan Jafree, W. Savindu Pasan Botheju, Yuxuan Mao, Anna Tomdio, Kristyn Gentry
Journal: Circulation (2022)

Introduction: Although Chagas disease affects over 300,000 residents in the US, donor-derived Trypanosoma cruzi transmission is an uncommon complication after heart transplantation. We present a case of post-transplant Chagas cardiomyopathy. Results: A 68 year old male with history of heart failure with reduced ejection fraction secondary to ischemic cardiomyopathy, status post HeartMate III and subsequent orthotopic heart transplantation from a Hispanic donor, initially presented four months after transplant for routine right heart catheterization. Endomyocardial biopsy showed grade 2R acute cellular rejection. Patient was treated with IV steroids and discharged. One month later, he presented with one week of fevers, malaise, non-tender erythematous patches on his upper body and hemorrhagic bullae on his buccal mucosa. Initial workup was notable for pancytopenia with WBC 1.3 x10e9/L, hemoglobin 10.3g/dL, and platelets 77 x10e9/L, troponin 3.47 ng/mL, NT-proBNP 11,331 pg/mL, and new right bundle branch block on electrocardiogram. Cardiac MRI showed extensive multifocal late gadolinium enhancement and pericardial exudates, suggestive of atypical infection. Despite treatment with Filgrastim and IVIG, the patient progressed to cardiogenic shock complicated by complete heart block requiring transvenous pacing, and ventricular tachycardia. On hospital day 5, a peripheral smear confirmed Trypanosoma cruzi with high parasite burden and amastigotes were visualized on a shave biopsy of his rash. Patient was initiated on Benznidazole. He was treated in the intensive care unit, where his course was further complicated by recurrent VT, for which he received an implantable cardiac defibrillator, and renal failure requiring hemodialysis. Conclusions: We present a case of suspected donor-derived Chagas Disease. In retrospect, this patient’s initial episode of acute rejection was most likely due to Chagas Disease. Due to increasing globalization of endemic diseases and life-threatening complications associated with this disease, a high index of suspicion is required to diagnose and treat T. cruzi after heart transplantation in the setting of non-specific symptoms.
Abstract 14718: Using Renal-Specific Cyclo-Oxygenase-2-Deficient Mice to Understand the Pro-Thrombotic Effects of Non-Steroidal Anti-Inflammatory Drugs
Authors: Maria Lopes Pires, Plinio Ferreira, Fisnik Shala, Neringa Cypaite, Maria Vinokurova, Elizabeth Want, Harvey Herschman, Jane A Mitchell, Nicholas Kirkby
Journal: Circulation (2022)

Introduction: Non-steroidal anti-inflammatory drugs (NSAIDs) work by inhibiting the enzyme cyclooxygenase (COX)2 but their use increases thrombotic risk. We have shown that COX2 inhibition increases plasma methylarginines ADMA and LNMMA in mice and man. Methylarginines are controlled in the kidney but circulate causing inhibition of anti-thrombotic vascular NO by competing with L-arginine for the active site of eNOS. However, the causative links between renal COX2 (which is expressed predominately in fibroblasts), methylarginines and thrombosis remain unproven. Hypothesis: Here we hypothesised that deletion of COX2 from fibroblasts would result in a renal-specific COX2-deficiency and be sufficient to increase methylarginine levels and drive vascular NO dysfunction and a pro-thrombotic phenotype. Methods: Fibroblast COX2-deficient mice were generated from Fsp1-Cre and Ptgs2 flox strains. COX2 levels were measured by RT-qPCR, methylarginines by LC/MS/MS, vascular NO function as acetylcholine-induced dilation by myography and thrombosis in vivo after FeCl 3 -carotid injury. Results: Fibroblast COX2-deficient mice showed reduced COX2 expression in the renal medulla (Fig A) but not renal cortex, aorta, lung, colon, thymus or brain. This was associated with increased plasma ADMA and LNMMA levels (Fig B) and reduced NO-dependent dilatation of carotid arteries (Fig C). Fibroblast COX2-deficiency accelerated thrombosis after carotid artery injury which could be reversed by pre-treating animals with L-arginine (50mg/kg; 5 days) which displaces methylarginines from eNOS (Fig D). Conclusions: These data provide the first direct demonstration that renal COX2 regulates methylarginine levels to control systemic endothelial and thrombotic function. As such, they indicate that inhibition of renal COX2 contributes to the thrombotic risk seen in patients taking NSAIDs and suggest L-arginine supplementation as a potential rescue therapy to mitigate this.